Studies of transformed rabbit cell lines have concentrated on lines transformed using the human retroviruses HTLV-I and on the use of different rabbit lines as host for infection with HIV-1. A number of lines have been derived by in vitro transformation with HTLV-1. Eight of these lines were studied in great detail and characterized according to morphology, cell surface markers and basic functional properties. It was found that several of the lines were distinctly macrophage in character while others were more T-cell like. These lines are being introduced into rabbits either into the autologous hosts or into other MHC matched or unmatched rabbits. Preliminary results suggest that certain of these lines cause leukemia like symptoms and can result in death of the rabbit if sufficient numbers of live cells are introduced. All of the cell lines that were derived may be infected with HIV-1 but there is a large variation in the levels of HIV-1 p24 production. In order to determine whether CD4 is the cell surface receptor for HIV-1 in the rabbit, some of the HTLV-I lines that poorly supported infection with HIV-1 were transfected with human CD4. One of these lines showed a 5 to 6-fold increase in the amount of p24 production in the transfectant over the parent cell line. In addition, it was shown that HIV-1 infection of all of the lines, both the parents and the transfectants could be blocked using soluble human CD4. One line with macrophage characteristics was shown to be positive for HIV-1 infection by p24 production, by electron microscopy and by production of viral proteins but reverse transcriptase activity could not be detected in the assay used. It was found that this cell line produced a factor that interferes with the reverse transcriptase assay. This factor was partially characterized as a nuclease that destroys both substrate and products of the reverse transcriptase reaction. The inhibitor has also been found in normal macrophage cultures of both rabbit and human origin, as well as in some human cell lines such as U937.